A clinical, molecular genetics and pathological study of a FTDP-17 family with a heterozygous splicing variant c.823-10G>T at the intron 9/exon 10 of the MAPT gene.
Aged
Brain
/ diagnostic imaging
Chromosomes, Human, Pair 17
/ genetics
Exons
/ genetics
Female
Frontotemporal Dementia
/ diagnostic imaging
Genetic Association Studies
/ methods
Heterozygote
Humans
Introns
/ genetics
Magnetic Resonance Imaging
Male
Middle Aged
Motor Neuron Disease
/ genetics
Neuroimaging
Parkinsonian Disorders
/ diagnostic imaging
Point Mutation
/ genetics
Tauopathies
/ genetics
tau Proteins
/ genetics
Frontotemporal dementia
Genetics
Intron 9/exon 10 mutation
Neuropathology
c.823-10G>T
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
23
12
2020
revised:
17
04
2021
accepted:
13
05
2021
pubmed:
19
7
2021
medline:
1
1
2022
entrez:
18
7
2021
Statut:
ppublish
Résumé
We report the first clinical-radiological-genetic-molecular-pathological study of a kindred with c.823-10G>T MAPT intronic variant (rs63749974) associated with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We describe the clinical spectrum within this family and emphasize the association between MAPT gene variants and motor neuron disease. This report of a second family with FTDP-17 associated with c.823-10G>T MAPT variant strongly supports pathogenicity of the variant and confirms it is a 4-repeat (4R) tauopathy. This intronic point mutation, probably strengthens the polypyrimidine tract and alters the splicing of exon 10 (10 nucleotides into intron 9) close to the 3' splice site.
Identifiants
pubmed: 34274155
pii: S0197-4580(21)00171-8
doi: 10.1016/j.neurobiolaging.2021.05.010
pii:
doi:
Substances chimiques
MAPT protein, human
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
343.e1-343.e8Subventions
Organisme : NINDS NIH HHS
ID : R01 NS076837
Pays : United States
Informations de copyright
Copyright © 2021. Published by Elsevier Inc.